What if my testosterone level is low What are the risks and benefits of testosterone therapy

Hypogonadism is a condition in which low levels of testosterone are found in association with specific signs and symptoms, including decreased desire (libido) and sense of vitality, erectile dysfunction, decreased muscle mass and bone density, depression, and anemia. When hypogonadism occurs in an older male, it is referred to as andropause, or androgen deficiency of the aging male. Hypogonadism is estimated to affect 2 to 4 million men in the United States, and its incidence increases with age. Only about 5% of affected males are being treated.

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Table 18 Treatment Options for Erectile Dysfunction

Administration Dosing

Oral: taken on demand

0.5-1.5 hr before intercourse, requires stimulation

25,50,100 mg, lower dose if > 65 yr, use newer protease inhibitors, erythromycin, keto-conazole with hepatic/renal failure; 78% pts prefer 100 mg. Use only once per 24 hr.

Success Rate

48-81%; varies with etiology of erectile dysfunction

Contraindications

Concomitant nitrate use, retinitis pigmentosa. When using concomitant alpha-blockers, pt should be on stable dose of alpha-blocker prior to starting sildenafil; start with 25 mg dose. Follow Princeton guidelines regarding use in CV pts.

Side Effects

HA in 16%, flushing in 10%, dyspepsia in 7%, visual disturbance in 3%, priapism uncommon. NAION (nonarteritic anterior ischemic optic neuropathy) and hearing loss have been reported in individuals taking PDE 5 inhibitors, but a causal relationship has not been identified. The risk factors for NAION are similar to those for ED, such as age > 50 yr, HT, increased cholesterol, and DM.

Another risk factor is a small cup-to-disk ratio. Pts should be advised to seek medical attention in the event of a sudden loss of vision in one or both eyes.

Hearing loss has also been reported in patients taking PDE-5 inhibitors. As with NAION, a causal relationship has not been established.

Mechanisms of Action

Phosphodiesterase type V inhibitor leads to increased cGMP, which stimulates cavernous small muscle relaxation.

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^ Table 18 Treatment Options for Erectile Dysfunction (Continued)

Mechanisms

Rx Administration Dosing Success Rate Contraindications Side Effects of Action

Vardenafil

Oral: taken on demand 25 minutes to 60 minutes before intercourse, requires stimulation

2.5 mg, 5 mg, 10 mg, 20 mg. Recommended starting dose in most pts is 10 mgs. Start at 5 mg in pts > 65 yr, lower doses when concomitant use with CYP3A4 inhibitors.

Improvements in SEP 2 (ability to penetrate) of

(10-20 mg) compared to 52% with placebo and maintenance of erection SEP 3 of 64-65% (10-20 mg) compared to 32% placebo.

Nitrates, retinitis pigmentosa; if using alpha-blockers, must be stable on alpha-blocker therapy and start with lowest dose of Vardenafil. Follow Princeton guidelines regarding use in cardiovascular pts. May increase QTc interval and thus avoid use in individuals with congenital QT prolongation and those taking Class IA or III antiarrhythm ics.

NAION—see sildenafil side effects.

Hearing loss—see sildenafil side effects.

Phosphodiesterase type V inhibitor leads to increased cGMP, which stimulates cavernous small muscle relaxation.

Intraurethral alprostadil

Small suppository placed into distal urethra via small applicator

125,250,500, 1000 |ig. Use only once per 24 hr.

30—66% success rate (NEJM 1997; 336:1)

Hypersensitivity to PGE1, pregnant partner, predisposition to priapism (leukemia, multiple myeloma, sickle cell).

Pain (penile, urethral, testicular, perineal) in 33%, lowers blood pressure in 3%, priapism, vaginal irritation in 10%.

Absorbed through urethral mucosa and stimulates arterial dilation and flow.

Intracavernous injection therapy with alprostadil

Direct injection into lateral aspect of corpora cavernosa, alternating sides with each injection

5 |jg to > 40 |-ig; dose depends on etiology of ED; test dose at 10 p.g; if suspect neurologic disease, use 5p.g test dose; use only once per

48-72 hr.

Average success rate 73% (Int J Impôt Res 1994;6:149; J Urol 1988; 140:66)

Known hypersensitivity to alprostadil. Pts at risk for priapism. Pts at increased risk: those on anticoagulants and with Peyronie's dz.

Prolonged erections in 1.1—1.3%, corporal fibrosis in 2.7%, painful erection in 15—30%, hematoma, ecchy-mosis in 1.5%.

Alprostadil stimulates cavernous small muscle relaxation, causes modulation of adenyl cyclase, increase in cAMP and subsequent free Ca2+ conc.

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Despite the reported benefits of testosterone replacement therapy, including improvement in libido, bone density, muscle mass, body composition, mood, red blood cell count, and cognition, its use remains controversial.

Despite the reported benefits of testosterone replacement therapy, including improvement in libido, bone density, muscle mass, body composition, mood, red blood cell count, and cognition, its use remains controversial. There remain concerns regarding the risks of hormone therapy, particularly with respect to the risk of effects on the prostate, both benign and cancerous disease, as well as cardiovascular risks.

There is no definitive data to support that testosterone-replacement therapy increases cardiovascular risk. In fact, studies of testosterone replacement therapy have not demonstrated an increased incidence of cardiovascular disease or events such as myocardial infarction, stroke, or angina. Large scale placebo controlled long-term studies are needed to assess the long-term cardiovascular risks of testosterone therapy.

The data on the effects of testosterone replacement therapy on lipid profiles are inconsistent. Supraphysio-logic (higher than normal) doses of androgens have been shown to decrease high-density lipoprotein (HDL) levels. However, when physiologic (normal) replacement doses of testosterone (both in the intramuscular and transdermal formulations) have been used, there appears to be no change or only a small decrease in HDL levels.

Higher levels of testosterone appear to stimulate ery-thropoiesis. It appears that injections are associated with a greater risk of erythrocytosis than topical preparations. In males receiving testosterone replacement therapy, the hematocrit or hemoglobin level should be monitored so that appropriate interventions, such as dose reduction, withholding of testosterone, therapeutic phlebotomy, or blood donation, may be performed if erythrocytosis occurs.

Testosterone replacement therapy has been associated with increases in prostate volume, primarily during the first 6 months of treatment. Despite the increase in size of the prostate there do not appear to be significant changes in voiding symptoms, urine flow rates, and postvoid residual volumes.

Controversy exists regarding the impact of testosterone replacement therapy on prostate cancer risk. Androgen ablation therapy remains one of the primary forms of therapy for metastatic prostate cancer. Despite the hormone responsiveness of prostate cancer there is no compelling data to associate the risk of developing prostate cancer with testosterone replacement therapy. There is also no compelling data to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism with supplemental testosterone therapy increases this risk. However, proper monitoring with measurement of PSA and digital rectal examination should promote the early diagnosis, thus potentially the cure, of most unmasked prostate cancers identified during testosterone treatment. The role of testosterone replacement therapy in hypog-onadal men who have undergone curative treatment for prostate cancer is also controversial. Historically, it was felt that testosterone replacement therapy was con-traindicated in men with a history of prostate cancer, but this is being challenged in the hypogonadal male who has been treated and cured of prostate cancer.

The currently used formulations of testosterone (intramuscular, gel, transbuccal, and patch) do not appear to have significant effects on liver function and routine monitoring of liver function is not necessary. Oral testosterone therapy, which is not FDA-approved in the United States, is associated with potential liver toxicity.

Testosterone replacement therapy has been associated with worsening of sleep apnea or with development of sleep apnea. This appears to be more common in men treated with intramuscular testosterone and who have other risk factors for sleep apnea.

Other reported adverse effects of testosterone therapy include: breast tenderness and swelling, decreased tes-ticular size, adverse effects on fertility (particularly with the intramuscular formulation related to its high peaks), skin reactions (primarily erythema and pruritus) with transdermal formulations, pain and swelling at the site of injection for intramuscular testosterone, fluid retention which is usually mild in nature, but may be clinically significant in men with congestive heart failure, acne, oily skin, increased body hair, and flushing.

Dealing With Erectile Dysfunction

Dealing With Erectile Dysfunction

Whether you call it erectile dysfunction, ED, impotence, or any number of slang terms, erection problems are something many men have to face during the course of their lifetimes.

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